A new study has revealed an additional role for Cyclin Dependent Kinase 9 (CDK9) in the regulation of DNA repair during cell division, a process critical for preventing cancerous tumor growth. Through phosphorylation, researchers simulated CDK9’s interaction with other proteins and genes involved in cell division and cancer progression.
The research utilized CRISPR/Cas9 technology to create an experimental line of HeLa cervical carcinoma cells lacking the 55kDa isoform of CDK9 (CDK9-55KO). Published in Oncogene, the study was led by Prof. Antonio Giordano, M.D., Ph.D., from Temple University’s Sbarro Institute for Cancer Research and Molecular Medicine.
CDK9, discovered by Giordano in 1994, is a versatile protein kinase often dysregulated in tumors. The study focused on the role of the CDK9-55kDa isoform in DNA damage response, a critical cellular process in cancer treatment.
Researchers, led by Dr. Luigi Alfano from the National Cancer Institute of Naples Pascale Foundation, revealed that the absence of CDK9-55 negatively affected the homologous recombination repair mechanism, crucial for maintaining DNA integrity and preventing mutations.
Through phosphoproteomic screening, the team identified protein substrates regulated by CDK9, including its interaction with Cell Division Cycle 23 (CDC23). CDC23, a subunit of the Anaphase Promoting Complex Cyclosome (APC/C), plays a key role in protein degradation linked to cancer progression.
The study demonstrated that CDK9 phosphorylates CDC23 on Serine 588, a prevalent phosphorylation site in tumors. This finding sheds light on how cells select repair mechanisms, emphasizing the importance of genetic information preservation to reduce cancer predisposition.
This breakthrough opens avenues for developing pharmacological inhibitors targeting CDK9. Giordano suggests these inhibitors could be used alone or in combination with existing drugs to enhance their anti-tumor effectiveness.
The research underscores the intricate relationship between CDK9 dysfunction, cell division, DNA repair, and cancer progression. Understanding these connections could lead to novel therapeutic strategies for targeting cancer at its molecular roots.
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1. Source: Coherent Market Insights, Public sources, Desk research
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